The ribosome, the machinery essential for protein synthesis, obviously plays a key role in cell growth and its synthesis is intimately connected to the regulation of cell proliferation both in prokaryotic and eukaryotic cells. When cells are stimulated to proliferate by various means, an increase in ribosome synthesis takes place as one of the very early events before actual cell proliferation occurs. The goal of this project is to understand how cells regulate the production of ribosomes in response to environmental conditions. It is known that synthesis of ribosomal RNA (rRNA) is central in determining overall synthesis of ribosomes, and hence, the investigator will concentrate on regulation of rRna synthesis. The PI will use the yeast Saccharomyces cerevisiae as a model system because of the ease of genetic manipulation and the available knowledge of rRna synthesis by RNA polymerase 1. He will continue to identify molecular components participating in the regulation of the state of these components participating in the regulation of rRNA synthesis. To elucidate the mechanisms of regulation, he will analyze the state of these components, the rDNA template, RNA polymerase 1, and various transcription factors, in cells with high and low rRNA synthesis. The nucleolus, the site for rRna synthesis and ribosome assembly, is obviously important for cell growth, but its structure is complex and its functional importance may not be fully appreciated. In fact, recent studies suggest its importance in cell aging. In addition to studies of rRNA synthesis, he will also study the structure and localization of the nucleolus in yeast. The proposed work is intended to make a contribution to the understanding of important nucleolar functions including ribosome synthesis and it's regulation.